This project will develop new morphological approaches to the resolution of several diverse problems in biomedical research. The approaches will be based on histo- and cytochemistry and backscattered electron imaging in a scanning electron microscope (SEM). The research problems addressed are: a) the structure of the intracellular apparatus for clearing foreign materials from the blood of the bone marrow; b) the mitotic capability of subepithelilial mesenchymal cells in developing limb bud; c) the structure of meiotic chromosomes; and d) the synaptic architecture of the cerebral cortex in gangliosidosis. These studies will employ newly assembled, "state of the art" instrumentation for operating the SEM in a mode called Backscattered Electron Imaging (BEI). This mode allows the viewing of the internal contents of cells and tissues, together with familiar surface structure. This capability adds virtually another dimension to the use of the SEM and will produce novel structural information in the electron microscope domain.